Usual Dose: Dosage needs to be titrated, using ventricular rate as the guide.
An initial loading dose of 0.5 milligrams/kg (500 micrograms/kg) infused over a minute duration followed by a maintenance infusion of 0.05 milligrams/kg/min (50 micrograms/kg/min) for the next 4 minutes is recommended. This should give a rough guide with respect to the responsiveness of ventricular rate.
After the 4 minutes of initial maintenance infusion (total treatment duration being 5 minutes), depending upon the desired ventricular response, the maintenance infusion may be continued at 0.05 milligrams/kg/min or increased step-wise (eg 0.1 milligrams/kg/min, 0.15 milligrams/kg/min to a maximum of 0.2 milligrams/kg/min) with each step being maintained for 4 or more minutes.
If more rapid slowing of ventricular response is imperative, the 0.5 milligrams/kg loading dose infused over a 1 minute period may be repeated, followed by a maintenance infusion of 0.1 milligrams/kg/min for 4 minutes. Then, depending upon ventricular rate, another (and final) loading of 0.5 milligrams/kg/min infused over 1 minute period may be administered followed by a maintenance infusion of 0.15 milligrams/kg/min. If needed, after 4 minutes of the 0.15 milligrams/kg/min maintenance infusion, the maintenance infusion may be increased to a maximum of 0.2 milligrams/kg/min.
In the absence of loading doses, constant infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes. Maintenance infusions (with or without loading doses) may be continued for as long as 24 hours.
The following table summarizes the above and assumes that 3 loading doses (the maximum recommended) are infused over 1 minute and incremental maintenance doses are required after each loading dose. There should be no 4th loading dose, but the maintenance dose may be incremented one more time. (See Table 1.)
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In treatment of supraventricular tachycardia, responses to Esmolol HCl usually (over 95%) occur within the range of 50 to 200 micrograms/kg/min (0.05 to 0.2 milligrams/kg/min). The average effective dosage is approximately 100 micrograms/kg/min (0.1 milligrams/kg/min) although dosages as low as 25 micrograms/kg/min (0.025 milligrams/kg/min) have been adequate in some patients. Dosages as high as 300 micrograms/kg/min (0.3 milligrams/kg/min) have been used, but these provide little added effect and increase the rate of adverse effects so doses greater than 200 micrograms/kg/min are not recommended. Dosage of Esmolol HCl in supraventricular tachycardia must be individualized by titration in which each step consists of a loading dosage followed by a maintenance dosage.
This specific dosage regimen has not been studied intraoperatively and, because of the time required for titration, may not be optimal for intraoperative use.
The safety of dosages above 300 micrograms/kg/min (0.3 milligrams/kg/min) has not been studied.
In the event of an adverse reaction, the dosage of Esmolol HCl may be reduced or discontinued. If a local infusion site reaction develops, an alternate infusion site should be used and caution should be taken to prevent extravasation. The use of butterfly needles should be avoided.
Abrupt cessation of Esmolol HCl in patients has not been reported to produce the withdrawal effects which may occur with abrupt withdrawal of beta blockers following chronic use in coronary artery disease (CAD) patients. However, caution should still be used in abruptly discontinuing infusions of Esmolol HCl in CAD patients.
After achieving an adequate control of the heart rate and a stable clinical status in patients with supraventricular tachycardia, transition to alternative antiarrhythmic agents such as propranolol, digoxin, or verapamil, may be accomplished.
A recommended guideline for such a transition is given below but the physician should carefully consider the labeling instructions for the alternative agent selected. (See Table 2.)
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The dosage of Esmolol HCl should be reduced as follows: 1. Thirty minutes following the first dose of the alternative agent, reduce the infusion rate of Esmolol HCl by one-half (50%).
2. Following the second dose of the alternative agent, monitor the patient's response and if satisfactory control is maintained for the first hour, discontinue Esmolol HCl.
The use of infusion of Esmolol HCl up to 24 hours has been well documented; in addition limited date from 24-48 hours (N=48) indicate that Esmolol HCl is well tolerated up to 48 hrs.
Intraoperative and Postoperative Tachycardia and/or Hypertension: In the intraoperative and postoperative settings it is not always advisable to slowly titrate the dose of Esmolol HCl to a therapeutic effect. Therefore, two dosing options are presented: Immediate control dosing and a gradual control when the physician has time to titrate.
Immediate Control: For intraoperative treatment of tachycardia and/or hypertension give an 80 milligrams (approximately 1 milligrams/kg) bolus dose over 30 seconds followed by a 150 micrograms/kg/min infusion, if necessary. Adjust the infusion rate as required up to 300 micrograms/kg/min to maintain the desired heart rate and/or blood pressure.
Gradual Control: For postoperative tachycardia and hypertension, the dosing schedule is the same as that used in supraventricular tachycardia. To initiate treatment, administer a loading dosage infusion of 500 micrograms/kg/min of Esmolol HCl for one minute followed by a four-minute maintenance infusion of 50 micrograms/kg/min. If an adequate therapeutic effect is not observed within five minutes, repeat the same loading dosage and follow with a maintenance infusion increased to 100 micrograms/kg/min (see previous text about Supraventricular Tachycardia).
Notes: 1. Higher dosages (250-300 micrograms/kg/min) may be required for adequate control of blood pressure than those required for the treatment of atrial fibrillation, flutter and sinus tachycardia. One third of the postoperative hypertensive patients required these higher doses.
2.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
The safety and effectiveness of Esmolol HCl in the pediatric patients have not been established.
Intravenous administration. It may be used to administer the appropriate Esmolol HCl loading dosage infusion by hand-eld syring while the maintenance infusion is being prepared.
Esmolol HCl is not compatible with Sodium Bicarbonate (5%) Injection, USP.